Impact of Plasma Lipids on β Cell Function and Insulin Sensitivity

NCT ID: NCT05181514

Last Updated: 2022-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-30
• Study Completion Date: 2021-12-01

Brief Summary

The investigators aim to evaluate whether and to what extent glucose tolerance, beta cell function, insulin clearance, and glucose metabolic fluxes change in response to an acute increase in plasma triglycerides during lipid infusion, independently of free fatty acid (FFA) levels, in nondiabetic subjects.

Detailed Description

Mild hypertriglyceridemia is associated with reduced glucose tolerance and increased risk of type 2 diabetes, independent of obesity, in both cross-sectional and prospective studies. It is unclear whether this association is direct or mediated by circulating lipid substrates of triglycerides (free fatty acids, or FFA) and which are the mechanisms involved.

To comprehensively examine the effects of mild acute hypertriglyceridemia on major glucose homeostatic mechanisms involved in diabetes progression, two dual-labeled oral glucose tolerance tests (OGTT) during 5-hour intravenous infusions of either 20% Intralipid or normal saline will be performed in healthy lean volunteers. Lipid-induced changes in glucose tolerance and insulin metabolism will be evaluated.

Conditions

Hypertriglyceridemia; Glucose Intolerance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Normal Saline

Participants will undergo a dual labeled, 3-h oral glucose tolerance test (OGTT) during i.v. infusion of normal saline

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: OTHER

Participants will receive a 5 h primed (375 mL/m2)-continuous (25 mL h-1 m-2) i.v. infusion of normal saline (Sodium Chloride 0.9%), together with a 5 h primed (28 µmol/kg)-continuous (0.28 µmol min-1 kg-1) infusion of 6,6-\[2H2\]glucose. After 2 h, participants will consume within 5 min an oral glucose drink consisting of 147 mL of 50% dextrose solution (wt/vol) enriched with 1.5 g of \[U-13C\] glucose.

20% Intralipid

Participants will undergo a dual labeled, 3-h oral glucose tolerance test (OGTT) during i.v. infusion of Intralipid 20%.

Group Type: EXPERIMENTAL

20% Intralipid

Intervention Type: OTHER

Participants will receive a 5 h primed (375 mL/m2)-continuous (25 mL h-1 m-2) i.v. infusion of 20% fat emulsion (Intralipid 20%), together with a 5 h primed (28 µmol/kg)-continuous (0.28 µmol min-1 kg-1) infusion of 6,6-\[2H2\]glucose. After 2 h, participants will consume within 5 min an oral glucose drink consisting of 147 mL of 50% dextrose solution (wt/vol) enriched with 1.5 g of \[U-13C\] glucose.

Interventions

20% Intralipid

Participants will receive a 5 h primed (375 mL/m2)-continuous (25 mL h-1 m-2) i.v. infusion of 20% fat emulsion (Intralipid 20%), together with a 5 h primed (28 µmol/kg)-continuous (0.28 µmol min-1 kg-1) infusion of 6,6-\[2H2\]glucose. After 2 h, participants will consume within 5 min an oral glucose drink consisting of 147 mL of 50% dextrose solution (wt/vol) enriched with 1.5 g of \[U-13C\] glucose.

Intervention Type: OTHER

Normal Saline

Participants will receive a 5 h primed (375 mL/m2)-continuous (25 mL h-1 m-2) i.v. infusion of normal saline (Sodium Chloride 0.9%), together with a 5 h primed (28 µmol/kg)-continuous (0.28 µmol min-1 kg-1) infusion of 6,6-\[2H2\]glucose. After 2 h, participants will consume within 5 min an oral glucose drink consisting of 147 mL of 50% dextrose solution (wt/vol) enriched with 1.5 g of \[U-13C\] glucose.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• age 18-65 years
• Body mass index (BMI) 18-35 kg/m2
• both women and men

Exclusion Criteria

• chronic or acute diseases
• any medications
• pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Azienda Ospedaliero, Universitaria Pisana

OTHER

Sponsor Role: lead

Responsible Party

Andrea Natali

Full Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea Natali, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pisa

Locations

Azienda Ospedaliero-Universitaria Pisana

Pisa, PI, Italy

Countries

Italy

Other Identifiers

Intralipid01

Identifier Type: -

Identifier Source: org_study_id